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. 2018 Oct 8;9:4149. doi: 10.1038/s41467-018-06650-y

Fig. 6.

Fig. 6

CerS6-dependent C16-ceramide generation mediates stress response to serum starvation. a Serum withdrawal elevates CerS6 in cultured cells with concomitant increase of p53 and p21 while CerS6 siRNA silencing prevents the p53 and p21 accumulation in response to serum withdrawal. b CerS6 siRNA silencing partially rescues G0/G1 cell cycle arrest upon serum starvation. c Serum withdrawal elevates C16-ceramide in A549 cells (48 h post-withdrawal); this effect was abrogated upon CerS6 silencing (mean ± SE; n = 3; *P < 0.001; #P < 0.05, ANOVA). d p53 is pulled down in complex with C16-ceramide from serum-starved A549 cells but not from serum-starved cells with silenced (siRNA) CerS6 (mean ± SE; n = 3; *P < 0.00001, ANOVA). e Proposed mechanism of p53 regulation by C16-ceramide: cellular stress elevates CerS6 in endoplasmic reticulum, leading to generation of C16-ceramide (C16); ceramide binds to p53, preventing its interaction with MDM2; this halts the p53 ubiquitination and degradation; resulting accumulation of p53 leads to its nuclear translocation and transcriptional activation of stress response proteins